TriangleNCT02435849 · CITED IN SOURCE DOCUMENTS
Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2024-02-13
This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment.
Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary)
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary)
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary)
Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT)
Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse
Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion
Duration of Remission (DOR)
Site of Involvement of Subsequent Relapse
Relapse-free Survival Per IRC Assessment
Event-free Survival Per IRC Assessment
Overall Survival (OS)
Percentage of Participants Attaining CR or CRi at Day 28 +/- 4 Days Post Tisagenlecleucel (CTL019) Infusion by IRC Assessment
Response as a Function of Baseline Tumor Burden (Tumor Load) in Main Cohort Only
Bone Marrow MRD Status by Flow Cytometry Per IRC Assessment
Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood by Day 28 Response by Independent Review Committee (IRC) Assessment
Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow by Day 28 Response by IRC Assessment
Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Peripheral Blood by Day 28 Disease Response Per IRC Assessment
Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Bone Marrow by Day 28 Response by IRC Assessment
Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC
Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019)
Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire
Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire
Develop a Score Utilizing Clinical and Biomarker Data and Assess Its Ability for Early Prediction of Cytokine Release Syndrome (CRS)
Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (C Reactive Protein & Ferritin)
Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers)
Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion
Percentage of Participants With Overall Remission Rate (ORR) - From Fraunhofer Institute Manufacturing Facility
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From Fraunhofer Institute Manufacturing Facility as Per IRC
Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood - Tisagenlecleucel Manufactured From Fraunhofer Institute
Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow - Tisagenlecleucel Manufactured From Fraunhofer Institute
All Collected Deaths
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: 1. Relapsed or refractory pediatric B-cell ALL 2. Adequate organ function 3. For relapsed patients, documentation of CD19 tumor expression within 3 months of study entry. 4. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening. 5. Life expectancy \> 12 weeks. 6. Karnofsky (age ≥16 years) or Lansky (age \< 16 years) performance status ≥ 50 at screening 7. Signed written informed consent and assent forms 8. Must meet the institutional criteria to undergo leukapheresis or have an acceptable, store leukapheresis product 9. Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site. 10. Cohort 1 only: 1. First relapse AND hypodiploid cytogenetics OR 2. First relapse AND t(17;19) with defined TCF3-HLF fusion OR 3. First relapse with any cytogenetics provided the relapse occurred ≤ 36 months of initial diagnosis AND MRD at end of reinduction therapy is ≥0.01% by flow cytometry (local assessment) Exclusion Criteria 1. Isolated extra-medullary disease relapse 2. Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded. 3. Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell \[sIg positive and kappa or lambda restricted positivity\] ALL, with FAB L3 morphology and /or a MYC translocation) 4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease 5. Treatment with any prior gene therapy product 6. Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy 7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening 8. Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening 9. Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). 10. Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines. 11. Patient has an investigational medicinal product within the last 30 days prior to screening. 12. Pregnant or nursing (lactating) women. 13. Women of child-bearing potential, defined as physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception for at least 12 months after the CTL019 infusion and after CAR T-cells are no longer present by qPCR on two consecutive tests 14. Sexually active males must use a condom during intercourse at least 12 months after the CTL019 infusion after CAR T-cells are no longer present by qPCR on two consecutive tests
- healthy Volunteers
- false
- maximum Age
- 25 Years
- sex
- ALL
- std Ages
- CHILD
- ADULT
Treatment arms and interventions
- arm Groups
- description
- Pediatric patients with relapsed or refractory B-cell ALL who were treated with single dose of tisagenlecleucel (CTL019).
- intervention Names
- Biological: CTL019
- label
- Single dose of CTL019
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Single dose of CTL019
- description
- Tisagenlecleucel was administered as a single iv infusion. Dose: 2.0 to 5.0x10\^6 tisagenlecleucel per kg body weight (for patients ≤ 50 kg) or 1.0 to 2.5x10\^8 tisagenlecleucel (for patients \>50 kg).
- name
- CTL019
- type
- BIOLOGICAL
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 80
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Evaluating the efficacy of tisagenlecleucel therapy from all manufacturing facilities as measured by overall remission rate (ORR) during the 3 months after tisagenlecleucel administration. ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee assessment. Per response criteria defined by National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH) and International Working Group (IWG) guidelines. CR is defined as: Bone marrow \<5% blasts, Peripheral blood: Neutrophils \>1.0 x 10\^9/L, and Platelets \>100 x 10\^9/L and Circulating blasts \<1% and No evidence of extramedullary disease, at least 7 days transfusion independency. CRi is defined as all the prior criteria being met, except that the following exists: Neutrophils ≤1.0 x 10\^9/L, and/or Platelets ≤100 x 10\^9/L, and/or Platelet and/or neutrophil transfusions ≤7 days before the date of the peripheral blood sample for disease assessment.
- measure
- Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment.
- time Frame
- during the 3 months after tisagenlecleucel administration
- secondary Outcomes
- description
- These are the percentage of participants with ORR who achieved overall remission rate which includes complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by IRC assessment after having been infused with tisagenlecleucel from US manufacturing facilities.
- measure
- Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary)
- time Frame
- 3 months after tisagenlecleucel administration
- description
- These are the percentage of participants who achieved Best Overall Response (BOR) of complete response (CR) or complete response with incomplete blood count recovery (CRi) with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from US manufacturing facilities only, by IRC assessment.
- measure
- Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary)
- time Frame
- 3 months after tisagenlecleucel administration
- description
- These are the percentage of participants who achieved Best Overall Response (BOR) of CR or CRi with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from all manufacturing facilities by IRC assessment. MRD negative = MRD% \< 0.01%
- measure
- Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary)
- time Frame
- 3 months after tisagenlecleucel administration
- description
- These are the participants who achieved CR or CRi without HSCT between tisagenlecleucel (CTL019) infusion and Month 6 response assessment.
- measure
- Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT)
- time Frame
- 6 months after tisagenlecleucel administration
- description
- These are the participants who achieved CR or CRi and then proceeded to HSCT while in remission prior to Month 6 response assessment
- measure
- Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse
- time Frame
- 6 months
- description
- These are the participants who achieved CR or CRi and then proceeded to SCT after being infused by tisagenlecleucel.
- measure
- Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion
- time Frame
- up to 6 months
- description
- DOR is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death.
- measure
- Duration of Remission (DOR)
- time Frame
- 60 months
- description
- Anatomical location of relapse in participants who achieved prior CR/CRi subsequent to tisagenlecleucel infusion.
- measure
- Site of Involvement of Subsequent Relapse
- time Frame
- 60 months
- description
- RFS is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death due to any cause during CR or CRi.
- measure
- Relapse-free Survival Per IRC Assessment
- time Frame
- 60 months
- description
- EFS is the time from date of tisagenlecleucel infusion to the earliest of death, relapse or treatment failure.
- measure
- Event-free Survival Per IRC Assessment
- time Frame
- 60 months
- description
- OS, is the time from date of tisagenlecleucel infusion to the date of death due to any reason.
- measure
- Overall Survival (OS)
- time Frame
- 60 months
- description
- These are participants who had a day 28 response (CR or CRi response) by IRC assessment.
- measure
- Percentage of Participants Attaining CR or CRi at Day 28 +/- 4 Days Post Tisagenlecleucel (CTL019) Infusion by IRC Assessment
- time Frame
- 1 month
Full study description
- brief Summary
- This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL.
- detailed Description
- This was a initially a one cohort, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL. This main cohort completed enrollment. Two new cohorts were added via an amendment, Cohort 1 for high risk B-cell ALL patients at first relapse, and Cohort 2 for feasibility and safety of CTL019 in high risk B-cell ALL in patients that relapsed \<6 months post allo-HSCT. Due to lack of recruitment, Cohort 1 and Cohort 2 halted recruitment. This decision was not related to any safety issue. The study had the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation \& Lymphodepleting Chemotherapy), Treatment and Primary Follow-up, Secondary Follow-up (if applicable) and Survival Follow-up. The total duration of the study is 5 years from CTL019 cell infusion. Efficacy analyses were performed only on the Main Cohort (n=79) who were infused with tisagenlecleucel. However, the data on disposition and demographics presented in this section includes all patients enrolled to the study (98) and all infused patients (80) (Main Cohort + Cohort 1). No patients were enrolled in Cohort 2.
Source references
- references
- citation
- Grupp SA, Maude SL, Rives S, Hiramatsu H, Baruchel A, Bader P, Bittencourt H, Buechner J, Laetsch TW, De Moerloose B, Qayed M, Stefanski HE, Davis KL, Driscoll TA, Nemecek E, Peters C, Yanik G, Balduzzi A, Boissel N, Khaw SL, Krueger J, Levine JE, Myers GD, Tiwari R, O'Donovan D, Awasthi R, Ramos R, Willert J, Pulsipher MA. Long-Term Clinical Outcomes of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory ALL. J Clin Oncol. 2026 Jul 29:JCO2501471. doi: 10.1200/JCO-25-01471. Online ahead of print.
- pmid
- 42525896
- type
- DERIVED
- citation
- Laetsch TW, Maude SL, Rives S, Hiramatsu H, Bittencourt H, Bader P, Baruchel A, Boyer M, De Moerloose B, Qayed M, Buechner J, Pulsipher MA, Myers GD, Stefanski HE, Martin PL, Nemecek E, Peters C, Yanik G, Khaw SL, Davis KL, Krueger J, Balduzzi A, Boissel N, Tiwari R, O'Donovan D, Grupp SA. Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial. J Clin Oncol. 2023 Mar 20;41(9):1664-1669. doi: 10.1200/JCO.22.00642. Epub 2022 Nov 18.
- pmid
- 36399695
- type
- DERIVED
- citation
- Laetsch TW, Maude SL, Balduzzi A, Rives S, Bittencourt H, Boyer MW, Buechner J, De Moerloose B, Qayed M, Phillips CL, Pulsipher MA, Hiramatsu H, Tiwari R, Grupp SA. Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2022 Jun;36(6):1508-1515. doi: 10.1038/s41375-022-01550-z. Epub 2022 Apr 14.
- pmid
- 35422096
- type
- DERIVED
- citation
- Thudium Mueller K, Grupp SA, Maude SL, Levine JE, Pulsipher MA, Boyer MW, August KJ, Myers GD, Tam CS, Jaeger U, Foley SR, Borchmann P, Schuster SJ, Waller EK, Awasthi R, Potthoff B, Warren A, Waldron ER, McBlane F, Chassot-Agostinho A, Laetsch TW. Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Blood Adv. 2021 Dec 14;5(23):4980-4991. doi: 10.1182/bloodadvances.2020003844.
- pmid
- 34432863
- type
- DERIVED
- citation
- Levine JE, Grupp SA, Pulsipher MA, Dietz AC, Rives S, Myers GD, August KJ, Verneris MR, Buechner J, Laetsch TW, Bittencourt H, Baruchel A, Boyer MW, De Moerloose B, Qayed M, Davies SM, Phillips CL, Driscoll TA, Bader P, Schlis K, Wood PA, Mody R, Yi L, Leung M, Eldjerou LK, June CH, Maude SL. Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia. J Immunother Cancer. 2021 Aug;9(8):e002287. doi: 10.1136/jitc-2020-002287.
- pmid
- 34353848
- type
- DERIVED
- citation
- Buechner J, Grupp SA, Hiramatsu H, Teachey DT, Rives S, Laetsch TW, Yanik GA, Wood P, Awasthi R, Yi L, Chassot-Agostinho A, Eldjerou LK, De Moerloose B. Practical guidelines for monitoring and management of coagulopathy following tisagenlecleucel CAR T-cell therapy. Blood Adv. 2021 Jan 26;5(2):593-601. doi: 10.1182/bloodadvances.2020002757.
- pmid
- 33496754
- type
- DERIVED
- citation
- Laetsch TW, Myers GD, Baruchel A, Dietz AC, Pulsipher MA, Bittencourt H, Buechner J, De Moerloose B, Davis KL, Nemecek E, Driscoll T, Mechinaud F, Boissel N, Rives S, Bader P, Peters C, Sabnis HS, Grupp SA, Yanik GA, Hiramatsu H, Stefanski HE, Rasouliyan L, Yi L, Shah S, Zhang J, Harris AC. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1710-1718. doi: 10.1016/S1470-2045(19)30493-0. Epub 2019 Oct 9.
- pmid
- 31606419
- type
- DERIVED
- citation
- Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866.
- pmid
- 29385370
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- acy of KYMRIAH in pediatric and young adults with r/r B-cell precursor ALL was evaluated in an open-label, multicenter single-arm trial (Study 1: CCTL019B2202; NCT02435849). In total, 107 patients were screened, 88 were enrolled, 68 were treated, and 63 were evaluable for efficacy. Nine percent of the enrolled patients did not re
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- ></ul></div></li><li>A subsequent study from the University of Pennsylvania reported the 3-year updated results of the global phase II <a href="/clinicaltrials/NCT02435849">ELIANA (NCT02435849)</a> trial that included 79 patients who were treated with tisagenlecleucel.[<a href="#cit/section_10.182">182</a>][<a href="/Common/PopU
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Preserved source evidence · Not medical advice